Abstract

Understanding intrathymic T cell differentiation has been greatly aided by the development of various reductionist in vitro models that mimic certain steps/microenvironments of this complex process. Most models focused on the faithful in vitro restoration of T cell differentiation and selection. In contrast, suitable in vitro models emulating the developmental pathways of the two major thymic epithelial cell lineages--cortical thymic epithelial cells and medullary thymic epithelial cells (mTECs)--are yet to be developed. In this regard, lack of an in vitro model mimicking the developmental biology of the mTEC lineage has hampered the molecular analysis of the so-called "promiscuous expression" of tissue-restricted genes, a key property of terminally differentiated mTECs. Based on the close biological relationship between the skin and thymus epithelial cell compartments, we adapted a three-dimensional organotypic coculture model, originally developed to provide a bona fide in vitro dermal equivalent, for the culture of isolated mTECs. This three-dimensional model preserves key features of mTECs: proliferation and terminal differentiation of CD80(lo), Aire(-) mTECs into CD80(hi), Aire(+) mTECs; responsiveness to RANKL; and sustained expression of FoxN1, Aire, and tissue-restricted genes in CD80(hi) mTECs. This in vitro culture model should facilitate the identification of molecular components and pathways involved in mTEC differentiation in general and in promiscuous gene expression in particular.

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call

Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.